A Prefrontal Cortex Map based on Single Neuron Activity

The intrinsic organization underlying the central cognitive role of the prefrontal cortex (PFC) is poorly understood. The work to date has been dominated by cytoarchitecture as a canvas for studies on the PFC, constraining concepts, analyses, results, and their interpretations to pre-configured delimitations that might not be relevant to function. We approached organization by profiling the activity and spatial location of >23,000 neurons recorded in awake mice. Regularly firing neurons were over-represented in most PFC subregions, yet a fine-grained activity map of the PFC did not align with cytoarchitecturally defined subregions. Instead, we observed a robust relationship between spontaneous activity patterns and intra-PFC hierarchy, suggesting internal organization principles transcending cytoarchitecture. Single neuron responses to sounds did not reflect intra-PFC hierarchy but were linked to spontaneous firing rate, indicating that responsiveness increases with excitability and is decoupled from the PFC’s intrinsic operational structure. Our data-driven approach provides a scalable roadmap to explore functional organizations in diverse brain regions and species, opening avenues to link activity, structure, and function in the brain.